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Malar J. 2016 May 10;15(1):264. doi: 10.1186/s12936-016-1318-2.

Delayed acquisition of Plasmodium falciparum antigen-specific CD4(+) T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis.

Author information

1
Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.
2
Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.
3
Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi.
4
Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
5
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
6
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. Kondwani.Jambo@lstmed.ac.uk.
7
Liverpool School of Tropical Medicine, Liverpool, UK. Kondwani.Jambo@lstmed.ac.uk.

Abstract

BACKGROUND:

Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood.

METHODS:

Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.

RESULTS:

There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.

CONCLUSION:

The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.

KEYWORDS:

CD4+ T cells; Cotrimoxazole; HIV-exposed children; Plasmodium falciparum

PMID:
27165269
PMCID:
PMC4862093
DOI:
10.1186/s12936-016-1318-2
[Indexed for MEDLINE]
Free PMC Article

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